1. Releasable Conjugation of Polymers to Proteins
Yuhui Gong, Jean-Christophe Leroux, Marc A Gauthier Bioconjug Chem. 2015 Jul 15;26(7):1172-81. doi: 10.1021/bc500611k. Epub 2015 Feb 9.
Many synthetic strategies are available for preparing well-defined conjugates of peptides/proteins and polymers. Most reports on this topic involve coupling methoxy poly(ethylene glycol) to therapeutic proteins, a process referred to as PEGylation, to increase their circulation lifetime and reduce their immunogenicity. Unfortunately, the major dissuading dogma of PEGylation is that, in many cases, polymer modification leads to significant (or total) loss of activity/function. One approach that is gaining momentum to address this challenge is to release the native protein from the polymer with time in the body (releasable PEGylation). This contribution will present the state-of-the-art of this rapidly evolving field, with emphasis on the chemistry behind the release of the peptide/protein and the means for altering the rate of release in biological fluids. Linkers discussed include those based on the following: substituted maleic anhydride and succinates, disulfides, 1,6-benzyl-elimination, host-guest interactions, bicin, β-elimination, biodegradable polymers, E1cb elimination, β-alanine, photoimmolation, coordination chemistry, zymogen activation, proteolysis, and thioesters.
2. Role of integrated cancer nanomedicine in overcoming drug resistance
Arun K Iyer, Amit Singh, Srinivas Ganta, Mansoor M Amiji Adv Drug Deliv Rev. 2013 Nov;65(13-14):1784-802. doi: 10.1016/j.addr.2013.07.012. Epub 2013 Jul 21.
Cancer remains a major killer of mankind. Failure of conventional chemotherapy has resulted in recurrence and development of virulent multi drug resistant (MDR) phenotypes adding to the complexity and diversity of this deadly disease. Apart from displaying classical physiological abnormalities and aberrant blood flow behavior, MDR cancers exhibit several distinctive features such as higher apoptotic threshold, aerobic glycolysis, regions of hypoxia, and elevated activity of drug-efflux transporters. MDR transporters play a pivotal role in protecting the cancer stem cells (CSCs) from chemotherapy. It is speculated that CSCs are instrumental in reviving tumors after the chemo and radiotherapy. In this regard, multifunctional nanoparticles that can integrate various key components such as drugs, genes, imaging agents and targeting ligands using unique delivery platforms would be more efficient in treating MDR cancers. This review presents some of the important principles involved in development of MDR and novel methods of treating cancers using multifunctional-targeted nanoparticles. Illustrative examples of nanoparticles engineered for drug/gene combination delivery and stimuli responsive nanoparticle systems for cancer therapy are also discussed.
3. Multicomponent synthesis of fully substituted thiazoles using glycine-based dithiocarbamates, acetic anhydride and nitroalkenes
Azim Ziyaei Halimehjani, Maryam Saeb, Maryam Khalesi Org Biomol Chem. 2022 May 11;20(18):3763-3766. doi: 10.1039/d2ob00448h.
Reaction of glycine-based dithiocarbamates with nitroalkenes in the presence of acetic anhydride was utilized for the synthesis of fully substituted 2-(alkylsulfanyl)-4-(nitroalkyl)-5-acyloxy-1,3-thiazoles. The reaction proceeds via the in situ formation of thiazol-5(4H)-one from glycine-based dithiocarbamates, followed by the Michael addition of this intermediate to nitroalkenes, aromatization, and esterification reaction cascade. This new one-pot three-component reaction afforded a diverse library of fully substituted thiazoles in high to excellent yields under solvent-free conditions.
